Advances in Trans-Epithelial Electrical Resistance (TEER) monitoring integration in an Intestinal Barrier-on-Chip (IBoC) platform with microbubbles-tolerant analytical method

Abstract

Trans-epithelial resistance (TEER) is one of the most widely performed analysis in vitro methods for monitoring barrier tissue development, formation and functional maturation. It is a basic and important tool for the reproduction of an artificial human epithelium. However, in the design and construction of organ on chip devices, the reliable TEER measurements still remain a challenge, in spite of their efficacy in providing real time information on tissue integrity and function. The observed limitations often concern the nature of the selected electrodes, made with opaque or metal materials that prevent microscopic investigation, their correct and stable reposition that affect the impedance spectroscopy analysis and microbubbles interference. Here, we present a method to perform real time TEER analysis on an Intestinal Barrier-on-Chip (IBoC) using integrated transparent electrodes, by means of impedance spectroscopy analysis and supported by a microbubble-tolerant calculation method. The human Caco-2 cells were used as an in vitro model of the intestinal epithelial cell barrier. Measurements can be carried out even in presence of microbubbles during the analysis, thus allowing application of this analytical method in microfluidic organ on chip devices that must perform in continuum for a long time.

Keywords

• Organ on chip
• Trans-Epithelial Electrical Resistance (TEER)
• Transparent biocompatible electrodes
• Gut monolayer on a chip
• Microbubbles in microfluidics